Betulinic Acid in Complex with a Gamma-Cyclodextrin Derivative Decreases Proliferation and in Vivo Tumor Development of Non-Metastatic and Metastatic B164A5 Cells

Betulinic acid, a very promising anti-melanoma agent, has very low water solubility that causes low bioavailability. To overcome this inconvenience, a highly water-soluble cyclodextrin was used (octakis-[6-deoxy-6-(2-sulfanyl ethanesulfonic acid)]-γ-cyclodextrin). The complex was physico-chemically analyzed using differential scanning calorimetry (DSC), X-ray and scanning electron microscopy (SEM) methods and then in vitro tested for its antiproliferative activity by the MTT assay and by cell cycle analysis. Finally, the complex was tested in vivo using an animal model of murine melanoma developed in C57BL/6J mice, where it caused a reduction in tumor volume and weight. The study revealed the beneficial influence of betulinic acid inclusion into the cyclodextrin in terms of antiproliferative activity and in vivo tumor development.     

Comparative Study of 9×19 mm Ammunition Combustion Products and Residues

During the last decades, authorities’ awareness on environmental and human health impact at national and international level has increased in the field of small arms ammunition containing lead and antimony. Thus, the evolution of environmental policies regarding production and use of heavy metals and their compounds, especially in EU countries, implied extensive studies on the environmental implications of 9×19 mm caliber ammunition use, especially in indoor shooting ranges. In this context, the paper describes the experimental studies performed on Pb‐containing conventional FMJ (full metal jacketed) ammunition and comparative measurements on new ammunition designed for training. The combustion products and residues from conventional Pb‐containing ammunition and Cu‐based “greener” ammunition were compared in terms of gaseous products, metal concentration in aerosols and metal concentrations in solid residues. Gas emissions and solid residues were measured for four different types of ammunitions. The results showed that the copper content of the residue is significantly higher in case of Cu‐containing composite bullets. For the ammunition equipped with Pb bullet, an important percentage of the Pb residue is generated by erosion of the exposed part of the bullet core. On the other hand, the ammunition containing Cu‐composite bullet generates large quantities of Cu residues, which have similar environmental impact and less impact on human health. Gas analysis indicated the presence of CO and NO_x and, surprisingly, high concentrations of HCN, CH₄, and NH₃. Lower gas concentrations are obtained for the composite bullets due to an incomplete combustion of gun propellant.     

Involvement of Microglia in the Pathophysiology of Intracranial Aneurysms and Vascular Malformations—A Short Overview

Aneurysms and vascular malformations of the brain represent an important source of intracranial hemorrhage and subsequent mortality and morbidity. We are only beginning to discern the involvement of microglia, the resident immune cell of the central nervous system, in these pathologies and their outcomes. Recent evidence suggests that activated proinflammatory microglia are implicated in the expansion of brain injury following subarachnoid hemorrhage (SAH) in both the acute and chronic phases, being also a main actor in vasospasm, considerably the most severe complication of SAH. On the other hand, anti-inflammatory microglia may be involved in the resolution of cerebral injury and hemorrhage. These immune cells have also been observed in high numbers in brain arteriovenous malformations (bAVM) and cerebral cavernomas (CCM), although their roles in these lesions are currently incompletely ascertained. The following review aims to shed a light on the most significant findings related to microglia and their roles in intracranial aneurysms and vascular malformations, as well as possibly establish the course for future research.     

M-Doped Al2TiO5 (M=Cr, Mn, Co) Solid Solutions and their Use as Ceramic Pigments

New ceramic pigments based on the tialite (Al₂TiO₅) structure, doped with Co (pink), Cr (green), or Mn (brown), were prepared through the pyrolysis of aerosols followed by calcination of the obtained powders at 1400°C. The expected decomposition of Al₂TiO₅ into a mixture of Al₂O₃ and TiO₂ on refiring was inhibited by Cr-doping and also by co-doping with Mg the Mn- or Co-doped samples. Microstructure and phase evolution during pigment preparation were monitored by scanning electron microscopy and XRPD. Unit cell parameters of tialite were determined by Rietveld refinement of the X-ray diffraction patterns, revealing in all cases the formation of solid solutions where the solubility of dopants in the Al₂TiO₅ lattice followed the trend Co3+ ions in a large interstitial site of the tialite lattice with a distorted octahedral geometry, and of Mn³⁺ and Co²⁺ ions in the Al³⁺ octahedral sites of the tialite lattice in the former case, and in both Al³⁺ and Ti⁴⁺ octahedral sites in the latter. Testing the ceramic glazes assessed the technological behavior of pigments, which found that the color stability was reasonably good for the Mn-doped tialite and the Cr-doped pigment, although the latter suffered a small loss of green hue. The Co-doped pigment was found to be not stable in glazes, undergoing a cobalt-leaching effect.     

Design,Synthesis, and Characterization of Macrocyclic Inhibitors of the Proprotein Convertase Furin

The activation of viral glycoproteins by the host protease furin is an essential step in the replication of numerous pathogenic viruses. Thus, effective inhibitors of furin could serve as broad-spectrum antiviral drugs. A crystal structure of an inhibitory hexapeptide derivative in complex with furin served as template for the rational design of various types of new cyclic inhibitors. Most of the prepared derivatives are relatively potent furin inhibitors with inhibition constants in the low nanomolar or even sub-nanomolar range. For seven derivatives the crystal structures in complex with furin could be determined. In three complexes, electron density was found for the entire inhibitor. In the other cases the structures could be determined only for the P6/P5-P1 segments, which directly interact with furin. The cyclic derivatives together with two non-cyclic reference compounds were tested as inhibitors of the proteolytic activation and replication of respiratory syncytial virus in cells. Significant antiviral activity was found for both linear reference inhibitors, whereas a negligible efficacy was determined for the cyclic derivatives.     

Anticancer Activity of Natural and Synthetic Chalcones

Cancer is a condition caused by many mechanisms (genetic, immune, oxidation, and inflammatory). Anticancer therapy aims to destroy or stop the growth of cancer cells. Resistance to treatment is theleading cause of the inefficiency of current standard therapies. Targeted therapies are the most effective due to the low number of side effects and low resistance. Among the small molecule natural compounds, flavonoids are of particular interest for theidentification of new anticancer agents. Chalcones are precursors to all flavonoids and have many biological activities. The anticancer activity of chalcones is due to the ability of these compounds to act on many targets. Natural chalcones, such as licochalcones, xanthohumol (XN), panduretin (PA), and loncocarpine, have been extensively studied and modulated. Modification of the basic structure of chalcones in order to obtain compounds with superior cytotoxic properties has been performed by modulating the aromatic residues, replacing aromatic residues with heterocycles, and obtaining hybrid molecules. A huge number of chalcone derivatives with residues such as diaryl ether, sulfonamide, and amine have been obtained, their presence being favorable for anticancer activity. Modification of the amino group in the structure of aminochalconesis always favorable for antitumor activity. This is why hybrid molecules of chalcones with different nitrogen hetercycles in the molecule have been obtained. From these, azoles (imidazole, oxazoles, tetrazoles, thiazoles, 1,2,3-triazoles, and 1,2,4-triazoles) are of particular importance for the identification of new anticancer agents.     

Studies on the Solvent Extraction of Rare Earth Metals from Fluorescent Lamp Waste Using Cyanex 923

The growing need for materials such as rare earth metals (REMs) has focused attention towards their recovery from various end-of-life products. Fluorescent lamps are considered a viable target, and can be a source of up to six REMs: lanthanum, cerium, europium, gadolinium, terbium, and yttrium. In this study a commercial mix of trialkylphosphine oxides (Cyanex 923) was investigated for the extraction of REMs from fluorescent lamp waste leachates. The kinetics of the extraction is addressed, together with the co-extraction of undesired elements (iron and mercury), the influence of temperature, nitric acid concentration in the aqueous phase and ligand concentration in the organic phase. The extraction of REMs was found to be enthalpically driven, with good separation factors between the light and heavier elements. Selective stripping of REMs was possible in a single step using 4 M hydrochloric acid solution. Further recovery of iron and mercury was carried out using nitric and oxalic acid solutions.     

Poly(2-hydroxyethyl methacrylate-co-dodecyl methacrylate-co-acrylic acid): synthesis,physico-chemical characterisation and nafcillin carrier

In the present study polymeric microbeads of poly(2-hydroxyethyl methacrylate-co-dodecyl methacrylate-co-acrylic acid) or p(HEMA-co-dDMA-co-AA) were synthesised and characterized through FT-IR and scanning electron microscopy (SEM); their swelling behavior against saline solution was explored and their in vitro cytotoxicity was evaluated. Further, in order to elucidate kinetic aspects regarding the ternary system p(HEMA-co-dDMA-co-AA), a mathematical model of the reactivity ratios of the comonomers in the terpolymer has been conceived and analyzed. An intensified tendency of AA units accumulation in the copolymer has been noticed, in spite of HEMA units, while dDMA conserves in the copolymer the fraction from the feed. Three compositions have been selected for nafcillin-loading and their in vitro release capacity was evaluated. The compositions of 80:10:10 and 75:10:15 M ratios appear suitable for further in vivo testing, in order to be used as drug delivery systems in the treatment of different osseous diseases.